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Your search keyword '"Tibbits, Glen F."' showing total 8 results
Start Over Author "Tibbits, Glen F." Journal physiological genomics
8 results on '"Tibbits, Glen F."'

7. Phylogeny of Na+/Ca2+ exchanger (NCX) genes from genomic data identifies new gene duplications and a new family member in fish species

Author

Marshall, Christian R., Fox, Joanne A., Butland, Stefanie L., Ouellette, B. F. Francis, Brinkman, Fiona S. L., and Tibbits, Glen F.

Abstract

The Na+/Ca2+ exchanger (NCX) is a member of the cation/Ca2+ antiporter (CaCA) family and plays a key role in maintaining cellular Ca2+ homeostasis in a variety of cell types. NCX is present in a diverse group of organisms and exhibits high overall identity across species. To date, three separate genes, i.e., NCX1, NCX2, and NCX3, have been identified in mammals. However, phylogenetic analysis of the exchanger has been hindered by the lack of nonmammalian NCX sequences. In this study, we expand and diversify the list of NCX sequences by identifying NCX homologs from whole-genome sequences accessible through the Ensembl Genome Browser. We identified and annotated 13 new NCX sequences, including 4 from zebrafish, 4 from Japanese pufferfish, 2 from chicken, and 1 each from honeybee, mosquito, and chimpanzee. Examination of NCX gene structure, together with construction of phylogenetic trees, provided novel insights into the molecular evolution of NCX and allowed us to more accurately annotate NCX gene names. For the first time, we report the existence of NCX2 and NCX3 in organisms other than mammals, yielding the hypothesis that two serial NCX gene duplications occurred around the time vertebrates and invertebrates diverged. In addition, we have found a putative new NCX protein, named NCX4, that is related to NCX1 but has been observed only in fish species genomes. These findings present a stronger foundation for our understanding of the molecular evolution of the NCX gene family and provide a framework for further NCX phylogenetic and molecular studies.

Published
2005

8. Familial hypertrophic cardiomyopathy-related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility.

Author

Liang B, Chung F, Qu Y, Pavlov D, Gillis TE, Tikunova SB, Davis JP, and Tibbits GF

Subjects
Animals, Biomechanical Phenomena, Cattle, Female, Glutamine genetics, Kinetics, Leucine genetics, Mice, Mice, Inbred C57BL, Mutant Proteins metabolism, Sarcomeres physiology, Actin Cytoskeleton physiology, Calcium metabolism, Cardiomyopathy, Hypertrophic, Familial genetics, Cardiomyopathy, Hypertrophic, Familial physiopathology, Mutation genetics, Myocardial Contraction physiology, Troponin C genetics
Abstract

The cardiac troponin C (cTnC) mutation, L29Q, has been found in a patient with familial hypertrophic cardiomyopathy. We previously showed that L29, together with neighboring residues, Asp2, Val28, and Gly30, plays an important role in determining the Ca(2+) affinity of site II, the regulatory site of mammalian cardiac troponin C (McTnC). Here we report on the Ca(2+) binding characteristics of L29Q McTnC and D2N/V28I/L29Q/G30D McTnC (NIQD) utilizing the Phe(27) --> Trp (F27W) substitution, allowing one to monitor Ca(2+) binding and release. We also studied the effect of these mutants on Ca(2+) activation of force generation in single mouse cardiac myocytes using cTnC replacement, together with sarcomere length (SL) dependence. The Ca(2+)-binding affinity of site II of L29Q McTnC(F27W) and NIQD McTnC(F27W) was approximately 1.3- and approximately 1.9-fold higher, respectively, than that of McTnC(F27W). The Ca(2+) disassociation rate from site II of L29Q McTnC(F27W) and NIQD McTnC(F27W) was not significantly different than that of control (McTnC(F27W)). However, the rate of Ca(2+) binding to site II was higher in L29Q McTnC(F27W) and NIQD McTnC(F27W) relative to control (approximately 1.5-fold and approximately 2.0-fold respectively). The Ca(2+) sensitivity of force generation was significantly higher in myocytes reconstituted with L29Q McTnC (approximately 1.4-fold) and NIQD McTnC (approximately 2-fold) compared with those reconstituted with McTnC. Interestingly, the change in Ca(2+) sensitivity of force generation in response to an SL change (1.9, 2.1, and 2.3 mum) was significantly reduced in myocytes containing L29Q McTnC or NIQD McTnC. These results demonstrate that the L29Q mutation enhances the Ca(2+)-binding characteristics of cTnC and that when incorporated into cardiac myocytes, this mutant alters myocyte contractility.

Published
2008
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